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Kuru is an acquired prion disease, transmitted through ritualistic cannibalism, that reached epidemic proportions in the Fore tribe of Papua New Guinea. In a previous post, I presented an article by John Collinge’s group on the selection process of heterozygosity at codon 129 of the prion protein gene (PRNP). The research group has gone a step further by recently describing a new polymorphism of the PRNP gene, G129V.
The authors performed PRNP genotyping of 3,000 individuals from the Eastern Highland population, which included 709 individuals who had participated in cannabalistic rituals. They looked specifically at the codons 127 and 129 among geographic regions and among individuals that were stratified by risk exposure (i.e., high, medium, and low risk).
The G127V variant was only found in those regions where kuru was prevalent. 127V was present in half of the women who had the highest exposure to kuru and who were homozygous for methionine at codon 129 (MM). Interesting, although 129V was present in kuru exposed populations, it was not found in those who succumbed to kuru or in unexposed population groups around the world. 127V was also invariably linked to a 129M allele and predominately found in 129MM homozygotes in contrast to 129MV heterozygotes. Heterozygosity at codon 127 thus conveyed resistance to kuru in others susceptible 129MM homozygotes.
Thus the newly described G127V polymorphism was naturally selected among populations exposed to kuru as a resistance factor. Both codon 129V and codon 127V are examples of natural selection that have occurred recently.
Once again, prion diseases teach us a lot about biology in general…hence another important factor for studying them.
Mead S, Whitfield J, Poulter M, Shah P, Uphill J, Campbell T, Al-Dujaily H, Hummerich H, Beck J, Mein CA, Verzilli C, Whittaker J, Alpers MP, & Collinge J (2009). A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure. The New England journal of medicine, 361 (21), 2056-2065 PMID: 19923577
